DE2346316C2 - Process for the preparation of 2-furylbenzimidazoles - Google Patents

Description

(Π)

in which Ri and R _{2 have} the meaning given above with an o-phenylenedlamine of the general formula III

NH

NH ₂

(UI)

wherein R and Rj have the meaning given above, in a polar organic solvent with exclusion of atmospheric oxygen and subsequent dehydrogenation of the azometal formed without its intermediate isolation In the presence of chlorine or oxygen and oxygen-transferring heavy metal complex catalysts, characterized in that both reaction steps are carried out at 10- 3O ⁰ C, if necessary, performed with cooling and the dehydrating agent in the second stage portions enters so as to initiate or that the above mentioned temperature range is not exceeded.

The invention relates to a process for the preparation of 2-Fury! -Benzlmldazoles of the general Formula I.

(D

Ri and Rj independently of one another hydrogen atoms, Ci-C ₄ -alkyl, benzyl, phenyl, C | -C ₄ -alkoxy groups, halogen atoms, cyano, nitro, Ci-d-alkylcarbonyl, dC ₄ -alkoxycarbonyl, dd-alkylsulfonyl-, SO, H-, COOH-. Cd-alkylcarbonylamino groups or an unsubstituted or substituted carbamoyl or sulfamoyl radical _{by one or two Ci-C 4 alkyl groups,}

Ri is a hydrogen atom, a Ci-C4-alkyl, Ci-d-alkoxy group, a chlorine atom, fluorine atom, a carboxy, Nitro. Phenyl, cyclohexyl or phenyl-Ci-d-alkyl group, or

R is a hydrogen atom, a Ci-C ^ alkyl group which can be substituted by a hydroxyl group, a chlorine atom, a cyano, Ci-C ₄ alkoxy, carbamoyl, carboxyl or Ci-C4 alkoxycarbonyl group; a cyclohexyl group; the benzyl radical, which can be substituted 1-imal by methyl groups, chlorine atoms or methoxy groups; a phenyl group which can be substituted 1-3 times by Ci-Cj-alkyl or Ci-Cj-alkoxy groups, chlorine atoms or bromine atoms, cyano or Ci-C ^ alkoxycarbonyl groups,
mean, by condensation of furan-2-aldehydes of the general formula II

(U)

Kl

wherein Ri and R] have the meaning given above, with an o-phenylenediamine of the general Formula HI

^m »

wherein R and R _{3 have} the meaning given above, In a polar organic solvent with exclusion of atmospheric oxygen and subsequent dehydrogenation of the azomethine formed without its intermediate isolation in the presence of chlorine or oxygen and oxygen-transferring heavy metal complex catalysts. The process is characterized in that both reaction steps are carried out at 10-30 ° C, if necessary with cooling, and the dehydration medium in the second stage is introduced in portions or introduced in such a way that the temperature range given above is not exceeded.

The 2-Furylbenzlmldazole are known (see. DE-OS 14 69 227, 15 45 846 and 15 94 841; corresponding to the US-PS 34 97 525 and 36 37 734) and represent valuable optical brightening agents.

Also the furan-2-aldehydes and aromatic o-dlamino compounds required as starting compounds are known from the above-mentioned patents.

The condensation of the furan aldehydes with the o-diamonds is expediently carried out in that the components in an approximately molar ratio until complete implementation, which is for example can be demonstrated by thin-film chromatography, stirred.

As a rule, it has proven to be advantageous to use a slight deficit (0.5 to 396) to use.

Suitable polar organic solvents are alcohols, ethers, esters, carboxamides, ketones and halogenated hydrocarbons.

Examples include selenium: methanol, ethanol, n-propanol, isopropanol, glycol, glycol monomethyl or 4 » -ethyl ether, glycol methyl ether, methylene glycol, Dloxan, tetrahydrofuran, dimethylformamide, glacial acetic acid, Acetonitrile, acetone, chloroform.

Water-miscible solvents are particularly preferred.

The dehydrogenation stage is expediently carried out in such a way that a solution or suspension is obtained of the azo-metal in the relevant organic solvent while stirring portloiiswelse the dehydrating medium enters until complete dehydration, which is also advantageous in thin-layer chromatography is pursued.

In addition to those mentioned above, non-polar solvents, such as, for. B. benzene, toluene, Chlorobenzene or o-chlorobenzene may be considered. The method according to the invention is preferably carried out as One-pot process, i.e. without intermediate isolation of the azometal and using one and the same like that Solvent for both reaction steps.

Preferred catalysts for carrying out the process according to the invention are cobalt and copper complexes of azomethines from aromatic o-hydroxy aldehydes such as salicyl aldehydes and aliphatic ones Diamonds like ethylenediamine.

They are expediently used in amounts of 0.1 to 5% (based on the furan-2-aldehyde).

The reaction with atmospheric oxygen can take place at normal pressure or elevated pressure, for example 0.5 to 200 atü, be performed.

The new process is distinguished from the methods known from the literature cited above high, d. H. almost quantitative expansion and excellent purity of the process products. It is on The following examples are explained in more detail. «)

example 1

252 g of 5- (2 ', 4'-dlchlorophenyl) -furan-2-aldehyde (96961 g) are suspended in 2000 ml of technical grade methanol. 175 g of 2-aminodilphenylamine (freshly _{distilled under N 2} , 99.596 g) are added under nitrogen at 20-25 ° C. and stirred for 5 hours with the highest possible stirring intensity under nitrogen at 20-25 ° C., with the aldehyde is converted in suspension to the yellow, crystalline azometal. A small sample is then taken, a little methanol and plenty of chlorine chloride are added to it, stirred and filtered. The filling advice must not

Show red-violet coloration; otherwise the 2-amino-diphenylamine is not yet fully implemented and the The stirring tent must be extended.

If the sample is OK, the nitrogen flow is switched off and cold water is added with external cooling and while stirring at 20-25 ° C gradually add 218 g of chloranil (96%) within 40 minutes, stir, 15 minutes and then add 2 g more chloranil at intervals of 10 minutes until one sample to which 2-amino-diphenylamine has been added turns purple.

The mixture is then left to stir for 30 minutes and the sample is repeated. Does it still show an excess of chloranil (Violet color), the batch is allowed to stir for a further 8 hours.

The crystalline precipitate is filtered off with suction, washed with 500 ml of technical grade methanol and then with water.

The crude product is carried to remove excess chloranil and adhering tetrachlorohydroquinone at 70 ° C in a mixture of 4000 ml of water, 900 g of 50% sodium hydroxide solution and 420 g of 38% bisulfite solution and heated for 30 minutes with stirring to 80-90 ° C. The crystalline precipitate is filtered off with suction while hot Washed 10,000 ml of water and dried at 60 ° C in a vacuum (melting point: 162-164 ° C). The yield is 374 g = 93% of theory and is thus almost twice as high as that according to the information from DE-OS 15 94 841 (Example 7) obtained yield.

Similar good results are obtained if one of the other aldehydes is used instead of the abovementioned aldehyde in DE-OS 15 94 841 listed 5-arylfuran-2-aldehydes, preferably 5- (3 ', 4'-Dlchlorphenyl) -furan-2-aldehyde, 5- (4'-chlorophenyD-furan-2-aldehyde, J- (4'-methylsulfonyl) -furan-2-aldehyde, 5- (4'-trifluoromethylphenyl) -furan-2-aldehyde, 5- <4'-cyanophenyl) -furan-2-aldehyde, 5- (4'-methoxycarbonylphenyl) -furan-2-aldehyde, 5- {4'-bromophenyl) -furan-2-aldehyde, 5- (4'-Acetylphenyl) -furan-2-aldehyde or 5- (4'-Nltrophenyl) -furan-2-aldehyde and instead des 2-AmIno-dlphenylamlns one of the other aromatic listed in DE-OS 15 45 846 and DE-OS 15 94 841 o-Dlamino compounds, preferably 1,2-diamino benzene, l-amino-2-methylamino-benzene, 1-amino-2-methylamino-5-methylbenzene, 4 ^ 611 ^ 1-2-8111 ^ 0 ^^ 116 ^ 13111 ^, 4-chloro-2-amlno-dlphenylaniln, 4-methoxy -2-amlnodlphenylamine, 4-cyano-2-aminodilphenylamine is used.

The dehydrating agent used can also be used with the same success, for example by trichlorobenzochinone, Tetracyano-benzoquinone, tetrabromobenzoquinone or tetrafluoroquinone and the solvent, for example replaced by ethanol, n-propanol, isopropanol, ethylene glycol or ethylene glycol monomethyl ether will.

Example 2

252 g of 5- (3 ', 4'-dichlorophenyl) -furan-2-aldehyde (96%) are suspended in 2000 ml of isopropanol. Under nitrogen 121 g of l-amino-2-methylamino-benzene are added at 20 ° C. and, if possible, at 20 ° C. for 7 hours -'5 stirred with high stirring intensity under nitrogen until a thin layer chromatogram (mobile solvent chloroform-ethyl acetate 1: 1) indicates the complete implementation of the diamond. Then the flow of solids is turned off and added Add 5 g of "salcomin" (cobalt complex of blsazometal from 2 moles of salicylaldehyde and 1 mole of ethylenediamine) and passing in a gentle stream of air at 20-25 ° C with stirring until thin-film chromatography (mobile solvent Ethyl acetate-chloroform) no azometal from chlorophenylfuran-aldehyde and 1-amino-2-methy'iamlnobenzene more available 1st.

The crystalline precipitate is then filtered off with suction and washed with isopropanol.

The mother liquor is concentrated to V _{3 of} its volume. The crystalline precipitate is filtered off with suction, washed with isopropanol and dried together with the crystal obtained first at 60 ° C. in vacuo. Melting point: 195-198 ° C.
The yield is 330 g, corresponding to 91% of theory.

According to the procedure given in DE-OS 15 45 846 (Example 6), the same components are used a total of only about 6296 of the theory of 2- (l'-methyl-benzimldazolyl- (2 ')) - 5- (3'-4'-dlchlorophenyl) -furan were obtained.

Example 3

31.4 g of 5- (methylsulfonyl) -furan-2-aldehyde and 17.5 g of 2-Amlnodlphenylamln (distilled under Ni) are in 300 ml of methanol were stirred for 20 hours at 10 ° C., the yellow crystalline azometal being completely formed. Without further inert gas protection, it is now added with continued cooling at 5-10 ° C. within about 1 Hour In small portions 21.8 g Chlcranll and then at intervals of about 10 minutes 0.5 g catfish at 10 ° C. further chloranil is added until a sample to which 2-aminodylphenylamine has been added turns violet in color. The mixture is then allowed to stir at 10 ° C. for a further 10 hours.

The crystalline precipitate is filtered off with suction, washed thoroughly with methanol and at 50 ^e C. I. Vac. dried. 44 g (94% of theory) of 2- (N-phenylbenzlmldazol-2-yl) -5- (p-methylsulfonylphenyl) -furan with a melting point of 228-230 ° C. are obtained.

^{6 (1} In the above example, if the reaction temperature is consistently 30 ° C, the reaction time for the Azomethln formation can be increased from 20 h to 3-4 hours, when the chloranil is introduced from 1 hour to 30 minutes and the subsequent stirring time from 10 to 3 hours The yield in this case is 91% of theory.

Claims (1)

Claim
Process for the preparation of 2-furyl-benzimidazoles of the general formula I. (D R, and R ₂ independently of one another are hydrogen atoms, Cd-alkyl, benzyl, phenyl, dd-alkoxy groups, halogen atoms, cyano, nitro, Ci-d-alkylcarbonyl, C, -C ₄ -alkoxycarbonyl, C, -C ₄ -Aikylsulfonyl-, SOjH-, COOH-, Ci-C ₄ -Alkylcarbonylamnogruppen or an unsubstituted or substituted by one or two Ci-C ₄ -alkyl radicals carbamoyl or sulfamoyl, R _{3 is} a hydrogen atom, a Ci-C ₄ -alkyl, Ci-C ₄ -alkoxy group, a chlorine atom, fluorine atom, a carboxy, nitro, phenyl, cyclohexyl or phenyl-Ci-Cj-alkyl group and R is a hydrogen atom, a Ci-C ₄ -alkyl group, which can be substituted by a hydroxyl group, a chlorine atom, a cyano, Ci-C ₄ -alkoxy, carbamoyl, carboxyl or Ci-C ₄ -alkoxycarbonyl group; a cyclohexyl group, the benzyl radical, which can be substituted 1-3 times by methyl groups, chlorine atoms or methoxy groups; a phenyl group which can be substituted 1-3 times by Ci-C ₄ -alkyl or Ci-C ₄ -alkoxy groups, chlorine atoms, bromine atoms, cyano, or Ci-C ₄ -alkoxycarbonyl groups,
mean,
by condensation of furan-2-aldehydes of the general formula II